A number of recent epidemiologic studies have been published which suggest that the consumption of fish by humans may offer protection against coronary heart disease. The mechanisms of this protection have not been fully elucidated. Previous work has focused on the effects of the polyunsaturated fatty acids of fish oil (i.e., eicosapentaenoic and docosahexaenoic acids) on platelet function and plasma lipid levels. Very little consideration has been given to the possible effects of fish oil constituents on the heart itself. This is surprising in view of the fact that modification of dietary fats can profoundly alter the lipid composition of cellular membranes in the myocardium. The overall aim of the present proposal is to examine the effects of dietary oil on myocardial membrane lipid composition, membrane structure and membrane function. Specifically, mitochondria, sarcoplasmic reticulum (SR) and sarcolemma (SL) will be isolated from hearts of rats fed varying amounts of menhaden oil (MO), a fish oil rich in n-3 polyunsaturated fatty acids. The content and fatty acyl composition of the major phospholipids will be determined in these isolated subcellular fractions and membrane structure (fluidity) will be evaluated using electron spin resonance spectroscopy. A variety of membrane and membrane-related functions will be studied in isolated subcellular membranes, isolated heart cells and isolated perfused hearts. Parameters to be examined include mitochondrial respiratory function, SR Ca++ uptake, SL Na++ - Ca++ exchange and alpha - and beta- adrenoceptor function. In addition to studying myocardial function we will further examine the effects of fish oil consumption on the response of the heart to an ischemic stress since preliminary studies in vivo indicate a protective effect of dietary MO on ischemic damage. Myocardial ischemia and reperfusion will be studied both in vivo and in isolated hearts to assess the contribution of cardiac versus extracardiac (i.e., platelets) mechanisms of protection. Biochemical parameters to be examined in ischemic hearts include the content of myocardial phospholipids, free fatty acids and long-chain fatty acyl coenzyme A and carnitine esters. The proposed studies will further our understanding of the effects of dietary fish oil on cardiac function and the pathogenesis of myocardial ischemia.